Process of preparing esters of n-car-bamylfumaramic acid



Patented Oct. 8, 1957 invention are N-carbamylmaleirnide,N-carbamylcitraconimide, N-carbamyl-alpha-ethylmaleirnide,N-carbamyl-dimethylmaleimide, N-(methylcarbamyl)-maleimide, N (nbutylcarbamyl) maleimide, N (tert. butyl- 5 carbamyl) maleimide, N(cyclohexylcarbamyl) maleimide, N (phenylcarbamyl) maleimide, N (tert.-butylcarbamyl) citraconimide and N (phenylcarbarnyl)-citraconimide.These yield, by the process of our invention, the corresponding transesters, viz., the N-carbamylfumaramates, the N-carbamylmesaconamates,the

N carbamyl alpha ethylfumaramates, and the N-carbarnyldimethylfumaramates. N carbamylrnaleimide is the preferredintermediate, and the preferred trans This invention relates to transN-carbamylamic esters N'carbamylamlc esters of thls mventlon are the N'derived from intramolecular anhydrides of cis Z-butenebamylfumaramates'Therefore carbamylmalelmlde dioic acids and the esters made therefromw1ll be used hereinafter in We have discovered that a new class fchemicals, describing and illustrating our invention, except where theN-carbamylimides derived from the cis Z-butenedioic Otherwise stated pyacids, react easily, in the presence of certain cis-trans T e a i n ofth N-carbamylfumaramates is illusisomerizing agents, with compoundswhich contain one trated as follows:

PROCESS OF PREPARING ESTERS OF N-CAR- BAMYLFUMARAMIC ACID Robert J.Kelly, Rutherford, and Carl E. Bryan, Fairlawn, N. J., assignors toUnited States Rubber (Iompany, New York, N. Y., a corporation of NewJersey No Drawing. Application November 30, 1953, Serial No. 395,284

4 Claims. (Cl. 260211) agent HO-C O0 or more non-tertiary carbinolgroups, i. e., primary or wherein R and R are the residues ofnon-tertiary alcosecondary alcoholic hydroxyl groups, to form the corre-40 hols, which can contain one or more additional hydroxyl spondingesters of unsaturated trans N-carbamylamic groups not involved in theesterification reactions A and acids. The reagent carbinol compoundshereinafter are B. The symbol n is an integer. called alcohols,regardless of the presence or absence of The N-carbamylfumaramic estersare formed simply, other substituent groups. The ease with which theimide either directly from N-carbamylmaleimide and an alcoring is openedin the new reaction is entirely unexpected as shOWIl in q tions A1 and13-1, or via theinterin view of the known stability, toward alcohols, ofthe mediate malelllic esters, as Shown in Equations sirnilarheterocyclicrings present in maleimide and phthaland in an ppr priate s l ent and inthe presence imid d th i N-alkylated d N-arylated d iv ti of anisomerizing agent. This solvent usually is the many of the known cyclicimides can actually be purified alcohol taking P in reaction an excessby recrystallization from alcohols without change. being used Over thatConverted to th st r.

Alternatively, we can prepare the trans N-carbamylamic 5 However, Whenthe reagent alcohol is 0116 W i h boils esters from the correspondingcis esters by the action of at a y high temperature at atmosPhel'icPressure, We an isomerizing agent, and we consider this process to beprefer to use the alcohol in little or no excess over that apart of ourinvention. However, for economic reasons amountheeded in theestefification, and to us With we usually prefer to prepare the transesters directly from it an inert Solvent Which bOils at a lowertemperature the alcohol and the N-carbamylimide in one operation. thanthe alcohol, thereby Simplifying the Process of P Th N- b li id hi h weemploye i our fying the ester. Furthermore, in the special cases in a tih h structure which we wish to react N-carbamylmaleimide withsubstantially all of the hydroxyl groups of a liquid polyhydric alcohol,or in which the alcohol is a solid which II NC ONHA melts or decomposesabove about 140 C., the use of an inert solvent is essential because theN-carbamylmaleimide, the alcohol, and/ or the desired product normallywherein A is hydrogen or a hydrocarbon group, and the are solidmaterials. p-Dioxan is a suitable solvent. remaining bonds are satisfiedby hydrogen or acyclic The temperature of the esterification and/orisomerihydrocarbon groups. These new N-carbamylimides are zation can bevaried over a wide range, e. g., from about prepared, as shown in detailhereinafter and in a coroom temperature (20 C.) to about C. The morepending application by Robert H. Snyder, Serial No. active alcohols suchas methanol and ethanol will react 367,108, filed July 9, 1953, which isa continuation-inwith N-carbamylmaleimide within a few minutes at roompart of his application Serial No. 312,870, filed October temperature,especially when the mixture is stirred 2, 1952, and now abandond, fromthe corresponding rapidly. The higher monohydric alcohols, e. g.,l-dodec- N-carbamylamic acids. anol, and the polyhydric alcohols reactwith N-carba- Typical N-carbarnylimides which are operable in ourmylmaleimide less rapidly, so that it is essential to heat U thereaction mixture in order to carry out the esterification in areasonable length of time. Above about 140 C. the yield of the desiredester decreases rapidly because of decomposition of N-carbamylmaleimide.For highest yield and purity of the ester we prefer to hold the reactiontemperature below about 110 C.

It is advisable to use substantially anhydrous reagents and solvents inour reaction because N-carbamylmaleimide reacts with water to formN-carbamylmaleamic acid. This competing hydrolysis -reaction usuallyappears to beat least as rapid as the"desiredesterification. Once theN-carbamylmaleamic acid is formed it cannot be esterified directly.Consequently,'while we can obtain asubstantial yield of, forexample,'ethylN carbamylfumaramate from 95% ethyl alcohol, we prefer touse absolute alcohol for maximum yield and' purity o the ester.

Typical alcohols which are operable in our invention are the monohydricaliphatic alcohols, e. g., methanol, ethanol, l-propanol, 2-propanol,l-butanol, '2-ethylhexan- 1-01, l-dodecanol, l-octadecanol; theunsaturated-alcohols, e. g., allyl alcohol and methallyl-alcohol; thehalogenated alcohols, e. g., ethylene chlorohydrin; the ether-acohols,e. g., ethylene glycol monomethyl ether and diethylene glycol monoethylether; the cycloa'lkyl-*alcohols, e. g., cyclchexanol; the 'aralkylalcohols, e.. g., benzyl alcohol; the tertiary-amino alcohols,-e. g.,triethanolamine; the cyanoalcohols, e. g., *beta-cyanoethanol; thealcohols formed by reduction of the carbon monoxide-olefin products made'by the 0x0 process; the hydroxy acids and esters, e. g., glycolic acid;the polyhydric-alcohols, e. g., ethylene glycol, the polyethyleneglycols, polymeric alcohols which have been formed by oxidizing'and thenpartially reducing isoolefinzconjugated diolefin copolymers, alkydresins having terminal alcoholic hydroxyls, glycerol, pentaerythritol,cellulose, starch, glucose, sucrose, s rbitol, polyvinyl alcohol, andpartial ethers and esters there of; monoglycerides; diglycerides;triglycerides containing one or more alcoholic hydroxyl groups,e."g.,'cast"roil and blown oils such as soya and linseed oils; methylolphenols, e. g., 2,6 dimethylol-4-alkyl-phenols and their condensationpolymers;'N-methylol compounds, e. g., N- methylolmaleimide and'N,N-dimethylolurea; and alcohols containing sulfone groups, e. g.,those alcohols made from a glycol and divinyl sulfone. Tertiary alcoholsare not'operable in our invention.

The N-carbamylfumaramic esters fall' into 'two very different groups:'those from monohydric alcohols, and those'from polyhydric alcohols. Asshown by P. O. Tawney in a copending'a'pplication Serial No. 395,282,filed November 30, 1953, now U. S. Patent No. 2,721,186, the transN-carbamylamic esters can be polymerized to form useful resins. Whileall of the trans N-carbamylamic esters will form such polymers, thetrans N-carbamylamic esters of polyhydric alcohols have a distinctiveproperty not possessed by trans N-carbamylamic esters of monohydricalcohols;namely, the extremely useful ability to form crosslinkedheteropolymers which can form' th'ermos'ettable coatings and castingswhich do not craze or shrink.

This valuable property can be used, for example, to make materials whichare similar to, butsuperior to, polystyrene. This resin is one of themost useful'of plastic materials. It is cheap, transparent, capable ofbeing dyed to form' beautiful, clear articles in many color shades,easily and rapidly moldable into any of many desirable shapes, etc.However, it has three major deficiencies; namely, it is soluble in manyorganic liquids, itis a permanently thermoplastic material which softensat so low a temperature that articles made from it' cannot be used aboveabout 90 C. and it is brittle. Tawney has further shown that thesedefects can be overcomeby copolymerizing styrene with one, or a mixtureof several trans N-ca'rb'amylamic' e'sters'of polyhydric alcohols.

Presumably, this improvement is due to the formation of athree-dimensional macromolecular structure. As styrene is onlydifunctional, it cannot homopolymerize to form such a structure.However, an ester containing at least two trans N-carbamylamic groups istetrafunctional, i. e., it can react with'a difunctional monomer to formthree-dimensional, i. e., crosslinked materials.

In making such crosslinked heteropolymers, Tawney prefers to use transN-carbamylamic esters of a particular type of polyhydric alcohol;namely, an alkyd'resin having terminal alcoholic hydroxyl groups. He hasfound that di-(N-carbamylfumaramic) esters made from such alkyds areespecially useful for making tough and rigid or slightly flexible solidheteropolymers.

The alkyd resin used in his invention can be made from anypolycarboxylic acid, or mixture thereof, and any polyhydric alcohol ormixture thereof, provided only that the reaction conditions and theproportions of the acidic and alcoholic reagents are such as to causethe alkyd chains to terminate with free hydroxyl groups rather than withfree carboxyl groups. Such alkyd resins and methods for making them are,of course, well known.

Typical polyca'rboxylic acids which can be used in making alkydssuitable for use in Tawneys invention are succinic acid, glutaric acid,adipic acid, pimelic acid, suberic acid, sebacic acid, maleic acid,citric acid, citraeonic acid, itaconic acid, aconitic acid, phthalicacid, isophthalic acid, terephthalic acid, 3,6-endomethylzne-1,2,3,6-tetrahydrophthalic acid and mixtures thereof. The anhydrides ofthese acids, when available, are equivalent to the acids in makingalkyds, and are generally used commercially in preference to the acidsfor economic reasons.

Typical polyhydric alcohols used in making the alkyds are ethyleneglycol, propylene glycol, diethylene glycol, glycerol,1,2,4-butanetriol, and mixtures thereof.

The N-carbamylimides used in our invention are made, as described in acopending application by Snyder, Serial "No. 367,108, filed July 9,1953, which is a continuationin-part of his application, Serial No.312,870, filed October 2, 1952 (now abandoned), from the correspondingN-carbamylamic acids. "Each of these is made from the anhydride of theappropriate 'dicarboxylic acid and a'urea. A preferred method ofcarrying out the latter reaction is described in a copending, but nowabandoned, application by Snyder, Serial No. 312,869, filed October 2,1952. His method of making the N-carbamylamic acids and theN-carbamylirnides therefrom is illustrated as follows:

A solutionof 500g. of maleic anhydrideand 300 g. of urea in 1000 ml. ofglacial acetic acid is heated at 50' C. for l2'hours, during which timemaleuric acid begins to crystallize. The mixture is allowed to coolandis left overnight at room temperature. "Then the white crystallineproduct is filtered, washed with glacial acetic acid, and dried at 50 C.The'maleuric acid, 405 g. or 56% of theory, melts at l61l62 C. withdecomposition.

Similarly, a urea is reacted in glacial acetic acid with an equivalentamount of an intramolecular anhydride of another alpha-olefinicalkenedioic acid to give the appropriate N-carbamylamic acid. TypicalN-carbamylamic acids are the following:

N-carbarnylcitraconamic acid, M. P. 149 C., N-(n-butylcarbamyl)-maleamic acid, M. P. 105.5107.0 C.,N-(tert.-butylcarbamyl)-maleamic acid, M. P. 15l.5 153.5 C., andN-(phenylcarbamyl)-maleamic acid, M. P. 162463 C.

' The anhydrides from which the N-carbamylamic acids are made areintramole'cular and are derived from the corresponding cisalpha-butenedioic acids.

Typical anhydrides are maleic anhydr'ide,'citraconic'anhydride,alpha-ethylmaleic anhydride, and 'dimethylmaleic anhydride.

Theureas from which the N-carbamylamic acids are made 'areurea itself(NHzCONH'2) and N-rnond-hydro'carbon-substituted ureas. This substituentcan be any radical containing only carbon and hydrogen, such as analkyl, alkenyl, cycloalkyl, terpenyl, aralkyl, or aryl group. Typicalalkyl ureas are N-methylurea, N-ethylurea, N-propylurea,N-isopropylurea, N-n-butylurea, N- secbutylurea, N-isobutylurea,N-tert-butylurea, the N- amylureas, N-n-hexylurea, N-n-heptylurea,N-n-octylurea, N-(Z-ethylhexyD-urea, N-n-nonylurea, N-n-dodecylurea andN-n-octadecylurea. Typical alkenyl ureas are N- allylurea,N-methallylurea and N-crotylurea. A typical cycloalkylurea isN-cyclohexylurea. A typical terpenylurea is N-bornylurea. Typicalaralkylureas are N-benzylurea and N-phenethylurea. Typical aryl ureasare N- phenylurea, the three N-tolylureas and the two N-naphthylureas.

These N-carbamylamic acids are converted to the correspondingN-carbamylimides, as illustrated with maleuric acid:

A mixture of 50 parts of maleuric acid and 120 parts of glacial aceticacid is heated to about 80 C. Acetic anhydride (50 parts) is addedgradually to the stirred mixture, which is held at the same temperatureuntil practically all of the suspended maleuric acid has disappeared.The hot solution is filtered, and cooled to room temperature, causingcrystallization of a white product. This material, the new compoundN-carbamylmaleimide, melts at 157-158 C.

Similarly, each of other typical N-carbamylamic acids is converted tothe corresponding N-carbamylimide:

N-carbamylcitraconimide, M. P. 110-1l5 C.; N-(nbutylcarbamyD-maleimide,M. P. 66.568.0 C. (this white compound did not crystallize until thesolution was evaporated in vacuo to about half volume; it wasrecrystallized from a mixture of benzene and Skellysolve Ba petroleumfraction which is chiefly n-hexane); N- (tert-butylcarbamyl)-maleimide,M. P. 106.0l07.5 C. (this white compound also did not crystallize untilthe solution was evaporated in vacuo to half volume; it wasrecrystallized from carbon tetrachloride); N-(phenylcarbamyl)-maleimide,M. P. 140l41 C. (this pale yellow compound was recrystallized frombenzene).

The cis-trans isomerizing agent used in our invention is selected fromthe class consisting of aluminum chloride; strong mineral acids such assulfuric acid, hydrochloric acid and hydrobromic acid; and thenon-tertiary amines. However, these isomerizing agents are not entirelyequal among themselves as regards activity and efficiency.

Our preferred agent is aluminum chloride because it effectsisomerization rapidly and completely; i. e., without undesirable sidereactions. When the trans esters are prepared directly from an alcoholand an N-carbamylimide we prefer to use anhydrous aluminum chlm ride toprevent the above mentioned undesirable reaction between water and theimide. However, when the trans esters are prepared from thecorresponding cis esters we can use either the hydrated form or theanhydrous form of aluminum chloride optionally.

The strong mineral acids are much less active catalysts than aluminumchloride; i. e., the isomerization is very much slower, and much more ofthe acid is needed.

The amines vary greatly in catalytic activity, but in general they aremuch less active than aluminum chloride. They, also usually give a muchlower yield of the trans isomer because of undesirable competingreactions. In particular, they are suitable ordinarily only forisomerizing the preformed cis esters to the corresponding trans estersbecause many of the amines react with the N-carbamylimides to give othermaterials at the expense of the cis esters, i. e., not only is the yieldof the trans ester lowered but also the catalyst for isomerization isinactivated.

When aluminum chloride is used as the catalyst, either in the combinedesterificatiOrr-isomerization reaction or in the isomerization reactionalone, we have found that as little as about 0.5 part of the catalystper parts of the N-carbamylimide sometimes is adequate. However, inorder to accelerate the esterification as well as the isomerization wesometimes use as much as 10 parts of the catalyst with alcohols whichare sluggish in reacting with the N-carbamylimide. In general, we preferto use between one and eight parts of aluminum chloride. These amountsare exclusive of any water of hydration which may be present.

When the strong mineral acids are used, we customarily need a minimum ofabout 5 parts, exclusive of water, to effect isomerization in anyreasonable time.

The primary and secondary amines, our least preferred class ofcatalysts, vary so much in their ability to effect isomerization that nogeneralizations can be made, However, none are nearly as active as thealuminum chloride.

In contrast, such compounds as zinc chloride, ferric chloride andcadmium chloride do not isomerize these cis esters to the correspondingtrans esters.

The following examples illustrate our invention. All parts are byweight:

Example 1 Example 2 Anhydrous aluminum chloride (0.6 part) was dissolvedin 100 parts of methanol. Then 14.0 parts of powderedN-carbamylamaleimide was added to the solution. Within a minute or twothe white N-carbamylfumaramate be- 'gan to crystallize from thesolution, and heat was evolvedl During the next hour the mixture wasstirred intermittently. At the end of this period the reaction appearedto be over. The liquid, which had been cloudy because of the formationof tiny crystals of the ester, became clear, and the ester settledquickly to the bottom. It was then filtered, washed with alcohol andether, and dried. The yield of methyl N-carbamylfumaramate was 14.5parts, or 84.3% of theory.

Examples 1 and 2 illustrate our preferred method of preparing transN-carbamylamic esters. These examples also show that the order of mixingis not critical.

Example 3 Anhydrous aluminum chloride (0.01 part) was added to asolution of 0.5 part of methyl maleurate in 5 parts of methanol. Therewas an immediate evolution of heat; and a white crystalline productprecipitated. This product, after recrystallization from water, meltedat 225230 C. A mixed melting point showed that it was identical with themethyl N-carbamylfumaramate describedin Example 1.

Examples l-3 show that aluminum chloride is an extremely active catalystin forming the trans N-carbamyl amic esters. Each of the two alternateprocesses shown in these three examples is applicable to the preparationof all the trans N-carbamylamic esters. Of course, as already mentioned,the reaction conditions, e. g., the sol vent, time and temperature ofreaction, vary with variation of the reagents.

The experiment of Example 3 when repeated on a larg-j er scale showedthe yield of methyl N-carbamylfumaramate to be quantitative.

Example 4 A mixture of 5.6 parts of N-carbamylamaleimide and 32 parts ofethylene chlorohydrin was heated on the -7 steam bath. The solutionbecame homogeneous within 30 minutes. .Then, asheating was continued, awhite solid:began-crystallizing. At the end of hours total heating themixture was cooled to room temperature, filtered, washed with ether anddried in vacuo. The yield of 2-chloroethyl N-ca'rbamylfumaramate was 5.7parts, or 65% of theory. It melted at 180188 C. Afterrecrystallizationfrom. methanol it..melted.at 189.5190.5 C., and showed an ultra-violetabsorption peakat2200 A.

Analysis.Calcd. for C7H9N2O4Cl: nitrogen, 12.68%. Found: nitrogen,12.62%, 12.59%. p

,As 'no isomerization catalyst had been added deliberately, ithadbeenexpected that the cis ester, 2-chloroethyl N-carbamylmaleamate,would be formed. However, the cis ester melts at ll6119 C., and is muchmore soluble in organic. solvents than the trans. ester. Furthermore,all-of the trans N-carbamylamic esters which have. been analyzed withultra-violet light show an absorption peak atabout 2200 A.,whereas thecorresponding cisesters show the peak below 2000 A. This agrees with theobservation by Wassermann and Smakula, 'Z. physik. Chem., Section A,155, 368 (1931), that dimethyl fumarate shows a; peak. at about 2150 A.,while dimethyl maleate shows a-peak at about. 1900 A.

.The lotsof ethylene. chlorohydrin used in this example was nthenfoundto contain a considerable amount of hydrogen.chloride'dissolved init. This hydrogen chloride was the isomerization catalyst.

Example 5 Example'6 'To a mixture of 100 parts of N-carbamylmaleimide,93 parts of Z-nitro-l-butanol and 150 parts of dioxan was added 6.0parts of aluminum chloride. The stirred mixture was heated for 2% hoursat 8590 C. At the end of the first 1% hours additional dioxan (250parts) was added because so much solid material had separated. The solidwas filtered while hot, and washed with dioxan and then was suspended indilute aqueous hydrochloric acid in order to remove any unr'eactedN-carbamylamaleimide. The light tan product was filtered, washed withwater, and dried. :The yield of Z-nitro-butyl N-carbamylfumaramate,melting at 2l4216 C., was 72.3 parts, or 39% of theory.

Amzlysis.Calcd.v for CsHrsNaOs: nitrogen, 16.3%. Found: nitrogen,16.89%, 16.90%.

Example 7 A stirred mixture of 140 parts of N-carbamylmaleimide, 238parts of technical grade n-dodecanol, parts of aluminum chloride and 500parts of dioxan was heated at 8590 C.. for two hours, and then waspoured into 2500 parts of water to precipitate an oily solid. 'Thissolid was filtered and then suspended in stirred 95% ethyl alcohol inorder to separate the ester from the excess dodecanol. .The ester wasthen filtered, washed with alcohol, and dried. The n-dodecylN-carbamylfumaramate, anofi-white solidmelting at 152157 C., wasobtained in 49% yield, or 160 parts.

Example 8 Z-hydroxyethyl maleurate'was 'isomerized by aluminum chloridein ethylene glycol to v.LhydroxyethylN-carbamylfumaramate during heatingfor 30 minutes on the steam bath. The white product melted at 173-183"'C.

Example 9 2-propyl maleurate was isomerized to:2-propyl'N-carbamylfumaramate by the method shown in Example 8, except thatthesolvent was 2-propanol, and the heating was doneunder a. refluxcondenser. The white. product melted at 170-180 C.

.Examples 69 showseveralv other trans N-carbamylamic esters made by theaction of aluminum-chloride, our preferred catalyst.

Example 10 To a solutionoflO part of methyl maleurate in 3.0 parts ofacetic acid was added 0.1 part of concentrated sulfuric acid. Thesolution was heated at C. Within a few minutes methylN-carbamylfumaramate began to crystallize. Heating wascontinued for afewminutes longer and then the mixture was cooled and filtered. The productwas washed withalittle acetic acid and-dried. The yield of methylN-carbamylfumaramate was quantitative, M. P. 2l8-224 C. Amixed meltingpoint showed thatitwasidentical with the .newester formed in Example 1.

Example 11 To a warm solution of 5 parts of n-butyl-maleurate in 20parts of acetic acid was added 0.5 part of concentratedsulfuric acid..The solution was heated at 80-90 C. for several minutes, and was thenleft overnight at room temperature. The white, crystalline N-butylN-carbamylfumaramate was filtered, washed with acetic acid, and dried.Yield 3.0 parts,.or 60% of theory; melting point l66-l68 C.

Examples 10 and 11 illustrate the use of sulfuric acid as an isomerizingagent in our invention. They also show that an organic acid e. g.,acetic acid, can be used as the reaction mediumin isomerizing a cisester to the correspondingtrans ester, although not usable as themediumin our preferred method, because the acid and the alcohol wouldreact to'form a conventional ester simultaneously with the desiredreaction between the alcohol and the N-carbamylimide.

Example 12 In order to compare directly the various types of cata-'lysts used in our invention, each of five catalysts, 0.2 part, exclusiveof any water with the catalyst, was dissolved separately in 50 parts ofmethanol. Then powdered N-carbamylmaleimide, 5.0 parts, was added toeach solution. The solutions were shaken intermittently at roomtemperature. Disappearance of thesolid N-carbamylmaleimide was taken toindicate the completion of the formation of methyl maleurate.(Experiments not involving isomerization showed this assumption to bejustified.) As methyl N-carbamylfumaramate is soluble in methanol to theextent of less than 0.5% by weight, whereas methyl maleurate is ,quitesoluble, the first appearance of crystals was taken to be evidence ofincipient isomerization of the cis ester to the trans ester. (MethylN-carbamylfumaramate crystals look quite different fromN-carbamylmaleimide powder.) The two solutions con taining aluminumchloride became somewhat warm during the reaction. The others showed noheat evolution perceptible to the hand, and consequently catalyst wasadded at the end of the'firsttwo hours, as noted individually. Eachsolution was filtered after 22 hours at room temperature to remove themethyl N-carbamylfumaramate. This was washed with methanol, and thenwith ether, and dried at C. The filtrates from experiments C, D, E; i.e., those catalyzed bymaterials other than aluminum chloride, slowlyprecipitated more methyl N-carbamylfumaramate. This was filtered afterthree days additional standing, and was treated like the first crop.Still more of the ester .continued tov precipitate very slowly from thesecond filtrate oflexpen'ment E, and was filtered after a'tot'al' 'time'of "43 days. Even more ester precipitated exceedingly slowly from thethird filtrate of experiment E, but it was not weighed. 7 The effect ofthe several catalysts is shown as follows:

(2) When the preparation was repeated except that zinc chloride orferric chloride was added to the mixture the reaction was completedwithin a few minutes with Experiment A B C D E Catalyst A1013 AlCla-SHzO8 H01 H2SOA Piperidine Time to solution of all of 1 imide (min.) 50 45120 30 Time to first precipitation of trans ester (min) 4 10 120 160 130Time to apparent completion of reaction (mim). 30 50 5, 760 5, 760 61,920

(4 days) (43 days) Percentage yield:

(first crop 100 93 57 57 7 (second crop) none none 17 12 3 (third crop)none none none none 42 (total) 100 93 74 69 52 h After 2 hours, 1.7parts of 36% HO] added, making a total of 2.2 parts of 36% E01(equivalent to 0.8 parts of anhydrous H01).

b After 2 hours, 0.8 part of concentrated H2804 added, making a total of1.0 part. After 2 hours, 0.8 part of piperidine added, making a total of1.0 part.

Experiments show:

(1) Aluminum chloride is the most powerful catalyst.

(2) Hydrated aluminum chloride is substantially equivalent to anhydrousaluminum chloride.

(3) The. strong mineral acids elfect isomerization very slowly.

(4) Piperidine is a less efiicient catalyst in our preferred processthan the strong mineral acids.

Example 13 To a solution of 2.0 parts of methyl maleurate in 30 parts ofmethanol was added 0.15 part of piperidine. There was a slight evolutionof heat, and the solution became turbidflwithin a few minutes. Duringthe next 16 hours methyl .N-carbamylfumaramate precipitated slowly.Atthe end of that time it was filtered, washed and dried as shown inExample 12. The yield was 40% of theory. Additional methylN-carbamylfumaramate continued to precipitate very slowly from thefiltrate.

This example shows that piperidine isoperable, in a less preferred, formof our invention, namely, in the isomerization of a previously isolatedcis ester.

The cis N-carbamylamic esters used in our invention are made accordingto the method disclosed by Snyder and Tawney in their application,Serial No. 395,281, filed November 30,: 1953.

Typical ones are'shown in detail, as follows:

. Example A (1) A rnixture of 203 parts of N-carbamylmaleimide and 320parts of methanol was boiled under a reflux con- ESTERS OF MALEURIC ACIDEster Reac- Nitrogen Analysis Yield Melting Pt. tion (percent) Alcohol(per- C.) Time cent) (Hrs) Oalcd. Found 1. Ethanol 111-112 2 15.05 14.8415.01 2. 2-Propan0l 113-114 16 14.00 13.95 13.97 3. Ethylene glycol M 60131.0131.5 2 13.85 13.59 13.71

B 2-hydroxyethyl maleurate. b The reaction mixture was heated on thesteam bath without reflux.

Example C The following maleurate esters were made by boiling underreflux a mixture of N-carbamylmaleimide, the appropriate alcohol, zincchloride, and about six volumes of p-dioxan per volume of the sum of thereagents, for a few hours. The zinc chloride was used in the proportionof about 3 parts per 100 parts of the N-carbamylmaleimide. Most of thedioxan was removed in vacuo, causing the desired ester to crystallize.purified by recrystallization from an appropriate solvent, as shown:

ESTERS OF MALEURIC ACID MADE IN DIOXAN Ester Nitrogen Analysis Solventof Yield Melting Pt. (percent) Alcohol Recrystn. (per- (C.)

cent) Calcd. Found 1.1-Butan0l C01 47 95-99 13.09 13.25 13.332.1-Dodecanol ethanol 40 110-111 12.15 12.23 12.23 3. 2-Nitro'1-butanoldioxan-l-water. 50 106.5-108.2 4. Etlhylene chlorohyt0luene. 1 66116-119 12. 68 12.62 12. 84

rln.

air-dried methyl N-carbamylrnalearnate (methyl maleu- Example D rate)was obtained in yield (200 parts) as a white solid melting at 110-113 C.After recrystallization from methanol it melted at 113-114 C.

Analysis.-Calcd. for CsHsNzO-unitrogen, 16.29%. Found: nitrogen, 16.36,16.38%.

A mixture of 1.96 parts of N-(n-butylcarbamyl)-maleimide, 108 parts ofbenzyl alcohol and 0.05 part of zinc chloride was heated at -90 C. for30 minutes, and then was poured into ice water to precipitate the whiteThe ester was zjsoeneb "1.1 I benzyl "N-(n butylcarbamyl)-maleamate.After recrysta'l-lization from a mixture of esterand methanolit meltedat 65.5-66.5 C. 'Yield214 parts, or"78% of theory.

Example E A mixture of 3.92 parts of N-(tert-butylcarbamyl)- maleimide,2.16 parts of benzyl alcohol and 0.05"part"of zinc chloride was treatedlike the mixture shownin-Example D. The white benzylN-(tert-butylcarbamyl)- maleamate melted at 70.0-72.5 C. Yield 5.5parts, or 90% of theory.

Example F A mixture of 4.32 parts of N-(phenylcarbamyl)- maleimide, 10parts of isopropanol and 0.05 part of zinc chloride was heated at 75-85C. for 2.5 hours. On cooling the mixture the white isopropylN-(phenylcarbamyl)-maleamate crystallized. After recrystallization fromisopropanol, it melted at 132133 C. Yield 3.8 parts, or 71% of theory.

Typical trans N-carbamylamic esters which can be made by our process aremethyl N-carbamylfumaramate, ethyl "N-carbamylfumaramate, n-propylN-ca'rbamylfumaramate, isoprop'yl N-carbamylfumararnate, n-butyl N-carbamylfumaramate, sec-butyl N-carbamylfumaramate, isobutyl"N-carbamylfuma'ramate, -n-amyl N-carbamylfumaramate, n-hexylN-carbamylfumaramate, -n-heptyl N-carbamylfumaramate, n-octylN-carbamylfumaramate, 2-ethylhexyl N carbamylfumaramate, n decyl Ncarbamylfumaramate, -n dodecyl N carbamylfumaramate, n-tetradecylN-carbamylfumaramate, n-hexadecyl N-carbamylfumaramate, n-octadecylN-carbamylfumaramate, allyl N-carbamylfumaramate, methallylN-carbamylfumaramate, Z-hydroxyethyl N-carbamylfumaramate, 2-ethoxyethyl N-carbamylfumaramate, 2-chloroethy1 N- carbamylfumaramate,benzyl N-carbamylfumaramate, 2-(N-morpholino) -ethylN-carbamylfumaramate, 2- nitrobutyl N-carbamylfumaramate, ethylenebis-(N-carbamylfumaramate), propylene bis (N carbamylfumaramate),trimethylene bis-(N-carbamylfumaramate), the bis- (N-carbamylfumaramate)of diethylene glycol, monoand bis-(N-carbamylfumaramates) of alkydresins having terminal hydroxyl -groups, monoand poly-(N-carbamylfumaramates) of castor oil, monoand poly-(N-carbamylfumaramates) of blown oils, monoandpoly-(N-carbamylfumaramates) of cellulose, monoandpoly-(N-carbamylfumaramates) of starch, monoandpoly-(N-carbamylfumaramates) of glucose, monoandpoly-(N-carbamylfumaramates) of cellulose whichhas been partiallyesterifiedwith carboxylic acids or their anhydrides, monoandpoly-(N-carbamylfumaramates) of sucrose, monoandpoly-(N-carbamylfumaramates) of cellulose-which has been partiallyetherified, monoand 'poly- (N-carbamylfumaramates) of polyvinyl alcohol,monoand poly (N-carbamylfurnararnates) of parlubl. Co., New York (1952),vol. 1, part B, pp. 991-994.

tially hydrolyzed polyvinyl acetate, methyl N-carbamylmesaconamate,isopropyl N-carbamylmesaconamate, 2- ethylhexyl N carbamylmesaconamate,n octadecyl N- carbamylmesaconamate, allyl N-carbamylmesaconamate,2-hydroxye'thy1 N-carbamylmesaconamate, benzyl N- carbamylmesaconamate,ethylene bis-(N-carbamylmesaconamate), methyl N (methylcarbamyl)fumaramate isopropyl N-(me'thylcarbamyl)-furnaramate, methyl .N-(n-butylcarbamyl) fumaramate, isopropyLN (n-butylcarbamyl)-fumaramate,benzyl N (n butylcarbamyl)- fumaramate, isopropyl N-(tert-butylcarbamyl)-fumaramate, isopropylN-(tert-butylcarbamyl)-fumaramate,' isopropyl N (phenylcarbamyl)fumaramate, benzyl N- (phenylcarbamyl)-fumaramate and n-propylN-(phenylcarbamyl)-mesaconamate.

All of the aforesaid applications of Robert H. Snyder, Pliny O. Tawney,and Snyder and Tawney are owned by the present assignee of thisapplication, and are concerned with covering different inventions thanthat herein claimed.

Having thus described our invention, what we claim and desire to protectby Letters Patent is:

1. A method of preparing esters of trans N-earbamylamic acids whichcomprises heating N-carbamylmaleimide, and a compound containing anon-tertiary alcoholic hydroxyl group in the presence of acis-transisomerizing agent selected from the class consisting of aluminumchloride, strong mineral acids, and non-tertiary amines.

2. A method of preparing esters of trans N-carbamylamic acids whichcomprises heating N-carbamylmaleimide, and a compound containing anon-tertiary alcoholic hydroxyl group in the presence of aluminumchloride.

3. A method of; preparing non-tertiary'alcohol esters ofN-carbamylfumaramic acid which comprises heating the correspondingisomeric cis esters of non-tertiary alcohols in the presence of acis-trans isomerizing' agent selected from the class consisting ofaluminumchloride, strong mineral acids, and non-tertiary amines.

4. A method of preparing non-tertiary alcohol-esters ofN-carbamylfumaramic acid which comprises heating thecorrespondingisomeric cis esters of non-tertiary alcohols in the presence of aluminumchloride.

"References Cited in the file of this patent 1 UNITED STATES PATENTS'Valjavic Dec. 22, 1942 Adelson Nov. 27, 1951' Cavallito et al.: J. Am.Chem. Soc., vol. 63 (1941),

Rodd: Chemistry of Carbon Compounds, Elsevier

1. METHOD OF PREPARING ESTERS OF TRANS N-CARBAMYLAMIC ACIDS WHICHCOMPISES HEATING N-CARBAMYLMALEIMIDE, AND A COMPOUND CONTAINING ANON-TERTIARY ALCOHOLIC HYDROXYL GROUP IN THE PRESENCE OF A CIS-TRANSISOMERIZING AGENT SELECTED FROM THE CLASS CONSISTING OF ALUMINUMCHLORIDE, STRONG MINERAL ACIDS, AND NON-TERTIARY AMINES.